A ROS/glucose stimulated-responsive ADSCs-derived exosomes-release hydrogel system for diabetic wound healing

Abstract

With numerous attempts at chronic wound healing in recent years, significant challenges pertaining to diabetic wound healing have arisen. These challenges result from excessive oxidative stress, vulnerability to bacterial infection, and persistent inflammation during the healing process. In response to the lack of a specific exosomes-sustained release system tailored for diabetic wounds, a reactive oxygen species (ROS)/glucose dual-responsive stimulated exosomes-released self-healing antibacterial antioxidant conductive multifunctional hydrogel has been developed, utilizing a simplistic “one-pot” method. This innovative hydrogel is constructed from a harmonious blend of polydopamine grafted MXene (PMX), chlorogenic acid (CA), L-ascorbate-2-phosphate trisodium slat (L), and adipose-derived stem cells (ADSCs) derived exosomes (E) with phenylboronic acid modified flaxseed gum (LG-PBA), chemically cross-linked with polyvinyl alcohol (PVA) to generate dynamic phenylboronate ester bond, to obtain P-LP-PMX-CA-L@E hydrogel. It was further demonstrated that the ROS/glucose-responsive exosomes-released P-LP-PMX-CA-L@E hydrogel integrated system could reduce ROS and inflammatory response by repairing the electron transfer chain, thereby facilitating skin damage repair in a mouse type I diabetic model. In conclusion, the multifunctional P-LP-PMX-CA-L@E hydrogel, endowed with stimuli-responsive exosomes release capability, exhibits a promoting effect on the healing of chronic diabetic wounds and offers a localized exosomes dual-response release strategy for the treatment of type I diabetic wounds.